Bicyclo[3.1.1]hept-2-ene, 2,6,6-trimethyl-, phosphosulfurized

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of the registered substance in male Sprague-Dawley rats was estimated to be greater than 10,000 mg/kg bw. The registered substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.
The acute dermal median lethal dose (LD50) of the registered substance in New Zealand white rabbits was estimated to be greater than 3160 mg/kg bw. The registered substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

substance was tested above the limit dose; males used instead of females; missing data on animals

Principles of method if other than guideline:

Study was conducted using a method equivalent to OECD Testing Guideline 423 and meets acceptable scientific standards. Groups of five animals received doses up to 10,000 mg/kg bw of the registered substance in ethanol and were observed for 14 days. Mortality and clinical signs were recorded, and a gross necropsy was performed. As a result, it is considered that the study is providing a sufficient amount of data to conclude regarding the acute toxicity of the registered substance.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 209 - 245 g
- Fasting period before study: overnight

Route of administration:

oral: gavage

Vehicle:

ethanol

Details on oral exposure:

20 % ethanol used as a solvent

Doses:

Five dosages ranging from 34.6 g to 10,000 mg/kg bw

No. of animals per sex per dose:

Five male rats per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at one, four and 24 hours and then daily thereafter
- Necropsy of survivors performed: yes

Statistics:

None

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no deaths observed

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No gross alterations observed

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test substance in male Sprague-Dawley rats was estimated to be greater than 10,000 mg/kg body weight. The registered substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Male sprague-dawley rats were orally exposed by oral intubation to different doses of the test substance by a method similar to OECD guideline 423. Five dosage levels were used ranging from 34.6 g to 10,000 mg/kg of body weight. After the 14 days observation period no clinical observations were noted and there were no deaths at any of the concentrations. No gross alterations were noted during necropsy of the animals. It was therefore estimated that the LD50 was greater than 10,000 mg/kg bw. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

The study was considered as reliable with restriction as it was conducted on the registered substance (as defined in section 1.1) and meets acceptable scientific standards, but before the implementation of GLP and of the OECD Testing Guideline.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

substance was tested above the limit dose; missing data on animals

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data present beyond the species, strain and that both sexes were used

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped abraded abdominal skin
- Type of wrap if used: binders of rubber dam, gauze and adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansed with corn oil

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50, 200, 794, 3160 mg/kg bw

Duration of exposure:

24 hours

Doses:

50, 200, 794, 3160 mg/kg bw

No. of animals per sex per dose:

4 animals per dosage level. No data showing the number of sexes in each group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals observed at 1, 4 and 24 hours and then daily. Observations were for mortality and toxic effects.
- Necropsy of survivors performed: yes

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths observed at any dosage level

Mortality:

None

Clinical signs:

other: All animals showed slight or moderate erythema that never lasted beyond day 9. Desquamation noted at the 2 highest concentrations and edema and atonia observed in the highest. Severity and duration showed a dose response effect (see results table)

Gross pathology:

None observed

Signs of dermal irritation observed in male and female albino rabbits.

Observation interval (days)	50 mg/kg	200 mg/kg	794 mg/kg		3,160 mg/kg
	Erythema	Erythema	Erythema	Desquamation	Erythema	Edema	Atonia	Desquamation
1	+(4)	+(4)	+(3) ++(1)	-	+(2)++(2)	+(2)	-	-
2	-	+(1)	+(4)	-	+(2)++(2)	+(2)	-	-
3	-	-	+(4)	-	+(4)	-	+(1)	-
4	-	-	-	+(4)	+(3)	-	-	+(2)
5	-	-	-	+(3)	+(2)	-	-	+(2)
6	-	-	-	+(3)	+(1)	-	-	+(2)
7	-	-	-	+(3)	-	-	-	+(3)
8	-	-	-	+(1)	-	-	-	+(3)
9	-	-	-	-	-	-	-	+(1)

+ = slight

++ = moderate

+++ = severe

(x) = number of animals showing that effect

- = no toxicity observed

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for the test substance dermal exposure to rabbits is assumed to be >3160 mg/kg bw as no mortality was observed ar any of the tested concentrations. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Following a protocol equivalent to OECD guideline 402, New Zealand white rabbits were exposed dermally to the test substance. Four rabbits were tested at each of the four concentrations. Some slight to moderate clinical effects were observed following a dose dependent pattern, but had all disappeared before the end of the observation period. No mortality was observed at any of the concentrations indicating the LD50 for dermal exposure to the registered substance is greater than 3160 mg/kg bw. No gross alterations were observed after necropsy of the animals. The registered substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 160 mg/kg bw

Quality of whole database:

The study was considered as reliable with restriction as it was conducted on the registered substance (as defined in section 1.1) and meets acceptable scientific standards, but before the implementation of GLP and of the OECD Testing Guideline.

Additional information

The acute toxicity: oral of the registered substance was determined according to a method similar to OECD Guideline for Testing of Chemicals 423 with deviations. Male sprague-dawley rats were treated with doses ranging from 34.6 mg/kg bw to 10,000 mg/kg bw. All animals were subjected to gross necropsy. At dose 10,000 mg/kg bw there was no mortality, no abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test substance in the male Sprague-Dawley rats was estimated to be greater than 10,000 mg/kg bw.

The acute toxicity: dermal of the registered substance was determined according to a method similar to OECD Guideline for Testing of Chemicals 402 with deviations. Male and female New Zealand white rabbits were treated with doses ranging from 50 mg/kg bw to 3,160 mg/kg bw. All animals were subjected to gross necropsy. Some slight to moderate clinical effects were observed following a dose dependent pattern. At dose 3,160 mg/kg bw there was no mortality, no abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the registered substance in the male and female New Zealand white rabbits was estimated to be greater than 3,160 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Study was conducted using a method equivalent to OECD Testing Guideline 423 and meets acceptable scientific standards. The study was conducted on the registered substance.

Justification for selection of acute toxicity – dermal endpoint
Study was conducted using a method equivalent to OECD Testing Guideline 402 and meets acceptable scientific standards. The study was conducted on the registered substance.

Justification for classification or non-classification

The acute oral median lethal dose (LD50) of the test substance in male Sprague-Dawley rats was estimated to be greater than 10,000 mg/kg body weight. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

The acute dermal median lethal dose (LD50) of the test substance in New Zealand white rabbits was estimated to be greater than 3160 mg/kg body weight. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.